DESCRIPTION: The overall goal of the proposed project is to examine the significance of nicotine-induced cardiovascular changes in modulating perception of pain and aversiveness in men and women. The pain relieving properties of cigarette smoking and its principal pharmacologic ingredient, nicotine, have long been suspected, but inconsistently confirmed. This project will investigate these properties under controlled laboratory conditions, including improved methods for distinguishing sensory and affective components of the response to pain and multiple up-to-date methods of measuring pain response. This research should clarify confusion on the relationship between pain and smoking. Three major studies are proposed involving 270 subjects, men and women smokers and nonsmokers between the ages of 20-40. Nicotine will be administered using a transdermal (or placebo) patch. Various pain measurements will be made, and continuous physiological measurements will be made of blood pressure, heart rate, skin conductance, cardiac output, peripheral resistance, and other hemodynamic indices by means of impedance cardiography. The investigators propose to extend previous studies in this area by: (1 ) determining whether nicotine increases tolerance to aversive stimulation as a function of nicotine-induced elevations in blood pressure; (2) determining whether pharmacological blockade of nicotine-induced blood pressure increases prevents nicotine's anti-nociceptive effects; (3) determining whether nicotine manifests a differential effect on affective as compared to sensory/intensity ratings of laboratory-induced pain; (4) examining gender differences in the above effects; (5) determining whether the above effects are moderated by hormonal fluctuations by evaluating the effects of nicotine on pain and cardiovascular reactivity during different phases of the menstrual cycle; and (6) relating nicotine- induced elevations in plasma catecholamines and B-endorphin to blood pressure increases and pain ratings.